CURRENT TREATMENT PATTERNS AND SAFETY OUTCOMES IN RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML) WITH AN NPM1 MUTATION: A SYSTEMATIC LITERATURE REVIEW (SLR)
Author(s)
Frank Snopek, MS, PharmD1, Aishwarya Kulkarni, BS, MS2, Kadija Diawara, MPH3, Bhagyashree Oak, PhD4, Abigail Silber, MPH2, Matthew O'Hara, MBA5.
1Kura Oncology, Germantown, WI, USA, 2Trinity Life Sciences, Waltham, MA, USA, 3Kura Oncology, Newark, NJ, USA, 4Trinity Lifesciences, Billerica, MA, USA, 5Trinity Life Sciences, HINGHAM, MA, USA.
1Kura Oncology, Germantown, WI, USA, 2Trinity Life Sciences, Waltham, MA, USA, 3Kura Oncology, Newark, NJ, USA, 4Trinity Lifesciences, Billerica, MA, USA, 5Trinity Life Sciences, HINGHAM, MA, USA.
OBJECTIVES: Relapsed/refractory (R/R) acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (NPM1-m), present in about 30% of AML cases, remains difficult to treat and carries a poor prognosis. Despite NPM1 mutation prevalence, treatment patterns and safety reporting have not been systematically synthesized. This systematic literature review (SLR) aims to characterize treatment patterns and safety outcomes in adults with R/R NPM1-m AML.
METHODS: An SLR was conducted per PRISMA guidelines using PubMed and Embase searches of peer-reviewed, English-language publications from January 2019 through December 2024. Eligible studies reported R/R AML with NPM1-m or KMT2A-rearrangement; this analysis focuses on NPM1-m. Title and abstract screening used one human and one AI-assisted reviewer with human adjudication; full-text screening used two independent human reviewers.
RESULTS: Of 645 full-text articles screened, 82 met the inclusion criteria. Most were retrospective (68%, n=56) or clinical trials (27%, n=22); 5% (n=4) were prospective/cohort studies. Studies were primarily conducted in North America (n=35), Europe (n=25), and Asia (n=20). Forty-five of 82 studies reported NPM1-m outcomes; median age was 39-70.5 years, and female proportions ranged from 38-70%.
In the 45 NPM1-m studies, venetoclax-based regimens were most common (n=22); targeted therapies (n=9; menin inhibitors [ziftomenib, revumenib, DSP-5336], FLT3 inhibitors [gilteritinib], and IDH inhibitors) and chemotherapy (n=7) were assessed as monotherapy or combination regimens.
Safety was reported in 12 of 45 studies, but not by NPM1-m status. In the 6 studies reporting Grade ?3 adverse events, hematologic toxicities predominated with intensive chemotherapy.
CONCLUSIONS: The R/R NPM1-m AML evidence base was varied and rarely mutation-specific. With no therapy approved for R/R NPM1-m during the review period, treatment relied on venetoclax-based regimens. Safety was reported most commonly at the R/R AML level only. These gaps reflect a need for NPM1-m-specific evidence generation and for targeted and combination regimens with more complete safety characterization.
METHODS: An SLR was conducted per PRISMA guidelines using PubMed and Embase searches of peer-reviewed, English-language publications from January 2019 through December 2024. Eligible studies reported R/R AML with NPM1-m or KMT2A-rearrangement; this analysis focuses on NPM1-m. Title and abstract screening used one human and one AI-assisted reviewer with human adjudication; full-text screening used two independent human reviewers.
RESULTS: Of 645 full-text articles screened, 82 met the inclusion criteria. Most were retrospective (68%, n=56) or clinical trials (27%, n=22); 5% (n=4) were prospective/cohort studies. Studies were primarily conducted in North America (n=35), Europe (n=25), and Asia (n=20). Forty-five of 82 studies reported NPM1-m outcomes; median age was 39-70.5 years, and female proportions ranged from 38-70%.
In the 45 NPM1-m studies, venetoclax-based regimens were most common (n=22); targeted therapies (n=9; menin inhibitors [ziftomenib, revumenib, DSP-5336], FLT3 inhibitors [gilteritinib], and IDH inhibitors) and chemotherapy (n=7) were assessed as monotherapy or combination regimens.
Safety was reported in 12 of 45 studies, but not by NPM1-m status. In the 6 studies reporting Grade ?3 adverse events, hematologic toxicities predominated with intensive chemotherapy.
CONCLUSIONS: The R/R NPM1-m AML evidence base was varied and rarely mutation-specific. With no therapy approved for R/R NPM1-m during the review period, treatment relied on venetoclax-based regimens. Safety was reported most commonly at the R/R AML level only. These gaps reflect a need for NPM1-m-specific evidence generation and for targeted and combination regimens with more complete safety characterization.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA73
Topic
Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
Oncology, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)